The airway epithelium during infancy and childhood: A complex multicellular immune barrier. Basic review for clinicians

Abstract

The airway epithelium is a complex multicellular layer that extends from the nasopharynx to the small airways. It functions as an immune respiratory barrier during early life that develops, matures, and regenerates to adapt to the changes in the environment. While airway epithelial abnormalities have been identified in several clinical disorders, there is increasing interest in understanding its basic regulation and structure in humans. Indeed, recent advances in technology (e.g. single-cell analysis and new human airway epithelial cell models) have allowed us to identify additional cellular subtypes and functions that overall have greatly improved our understanding of the airway epithelium during health and disease. In this review we summarize key features of the airway epithelium including: 1) multilayer structure and cell heterogeneity; 2) adaptability to different environmental and developmental stimuli; 3) innate recognition; and 4) orchestration of immune responses. We discuss these features with a translational and clinical prospective focusing on the development of human respiratory immunity, particularly during early life.

Keywords: Airway epithelium; Immune response; Pathogenesis of airway dieseases.

Fig. 1.. Airway epithelial cell heterogeneity and adaptability.

(A) The airway epithelium is a pseudos- stratified structure with multiple cell types. (B) The dynamic multicellular structure of the airway epithelium allows adaptability to the environment including exposure to IL-13, viruses or hypoxia. Figure performed with BioRender.com.

Fig. 2.. Airway epithelial cell orchestration of immune responses.

The airway epithelium recognizes molecular patterns linked to conditions pathogenic for humans via innate receptors (e.g. toll-like receptors or TLRs). These signals are integrated to initiate and promote specific immune cascades including antiviral and allergic type 2 responses. Figure performed with BioRender.com.